Clinical trials of new medications often rely on subjective, observer-based ratings of side effects in the form of movement abnormalities to evaluate safety and tolerance of medication dosage. Imprecise ratings of adverse side effects have led to inconsistent results from these trials. Well-known adverse effects are extrapyramidal motor side effects (EPS), which can emerge within days of beginning treatment of antipsychotic drugs to treat schizophrenia, especially in the elderly. EPS symptoms include abnormalities in velocity scaling (VS) and motor steadiness or smoothness. We have shown in Phase I of this programmatic research that a system can be developed to reliably quantify these motor impairments during handwriting. In Phase II, we plan to expand the research started in Phase I toward developing an easy-to-use, quantitative system for monitoring drug-induced EPS. Specifically, the primary goals of Phase II are to conduct large- scale studies across several laboratories and clinics to examine generalizability of the measuring procedure and to examine the influence of treatment- and subject-related factors on outcome variables. The Phase II research plan consists of four experiments: (1) to examine effects of treatment-related variables on fine motor control during handwriting; (2) to examine effects of subject-related variables, such as demographics, and psychopathology on fine motor control during handwriting; (3) to examine the effects of task complexity on fine motor control during handwriting; and (4) to examine the generalizability of our findings across sites. Our long-term goal is to develop a general-purpose system for large-scale clinical trials that can readily be adopted in multi-center, clinical trials evaluating new drug safety and tolerance. From the perspective of the clinician, our handwriting movement analysis system will be a practical tool for screening and monitoring medication side effects in a variety of inpatient and outpatient neuropsychiatric settings. From an industry and governmental perspective, drug development will benefit from reliable and valid tools for assessing medication-induced side effects. The pharmaceutical industry would be able to reduce research and development costs if adverse effects of new medications could be measured quicker and more reliably than conventional methods. [unreadable] [unreadable] [unreadable]